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SPEN induces miR-4652-3p to target HIPK2 in nasopharyngeal carcinoma.
Cell Death & Disease ( IF 9 ) Pub Date : 2020-07-02 , DOI: 10.1038/s41419-020-2699-2
Yang Li 1 , Yumin Lv 1 , Chao Cheng 2 , Yan Huang 3 , Liu Yang 1 , Jingjing He 1 , Xingyu Tao 1 , Yingying Hu 1 , Yuting Ma 1 , Yun Su 1 , Liyang Wu 1 , Guifang Yu 4 , Qingping Jiang 5 , Shu Liu 6 , Xiong Liu 7 , Zhen Liu 1
Affiliation  

SPEN family transcriptional repressor (SPEN), also known as the SMART/HDAC1-associated repressor protein (SHARP), has been reported to modulate the malignant phenotypes of breast cancer, colon cancer, and ovarian cancer. However, its role and the detail molecular basis in nasopharyngeal carcinoma (NPC) remain elusive. In this study, the SPEN mRNA and protein expression was found to be increased in NPC cells and tissues compared with nonmalignant nasopharyngeal epithelial cells and tissues. Elevated SPEN protein expression was found to promote the pathogenesis of NPC and lead to poor prognosis. Knockdown of SPEN expression resulted in inactivation ofPI3K/AKT and c-JUN signaling, thereby suppressing NPC migration and invasion. In addition, miR-4652-3p was found to be a downstream inducer of SPEN by targeting the homeodomain interacting protein kinase 2 (HIPK2) gene, a potential tumor suppressor that reduces the activation of epithelial–mesenchymal transition (EMT) signaling, thereby reducing its expression and leading to increased NPC migration, invasion, and metastasis. In addition, SPEN was found to induce miR-4652-3p expression by activating PI3K/AKT/c-JUN signaling to target HIPK2. Our data provided a new molecular mechanism for SPEN as a metastasis promoter through activation of PI3K/AKT signaling, thereby stimulating the c-JUN/miR-4652-3p axis to target HIPK2 in NPC.



中文翻译:

SPEN诱导miR-4652-3p靶向鼻咽癌中的HIPK2。

SPEN家族的转录阻遏物(SPEN),也称为SMART / HDAC1相关阻遏蛋白(SHARP),据报道可调节乳腺癌,结肠癌和卵巢癌的恶性表型。然而,其在鼻咽癌(NPC)中的作用和详细的分子基础仍然难以捉摸。在这项研究中,与非恶性鼻咽上皮细胞和组织相比,NPC细胞和组织中的SPEN mRNA和蛋白表达增加。发现升高的SPEN蛋白表达促进NPC的发病机理并导致不良预后。敲低SPEN表达导致PI3K / AKT和c-JUN信号失活,从而抑制NPC迁移和侵袭。此外,通过靶向同源域相互作用蛋白激酶2(HIPK2)基因,发现miR-4652-3p是SPEN的下游诱导剂,它是一种潜在的肿瘤抑制因子,可减少上皮-间质转化(EMT)信号的激活,从而降低其表达和导致NPC迁移,侵袭和转移增加。另外,发现SPEN通过激活PI3K / AKT / c-JUN信号转导至目标HIPK2来诱导miR-4652-3p表达。我们的数据通过激活PI3K / AKT信号传导为SPEN作为转移启动子提供了新的分子机制,从而刺激c-JUN / miR-4652-3p轴靶向NPC中的HIPK2。和转移。另外,发现SPEN通过激活PI3K / AKT / c-JUN信号转导至目标HIPK2来诱导miR-4652-3p表达。我们的数据通过激活PI3K / AKT信号传导为SPEN作为转移启动子提供了新的分子机制,从而刺激c-JUN / miR-4652-3p轴靶向NPC中的HIPK2。和转移。另外,发现SPEN通过激活PI3K / AKT / c-JUN信号转导至目标HIPK2来诱导miR-4652-3p表达。我们的数据通过激活PI3K / AKT信号传导为SPEN作为转移启动子提供了新的分子机制,从而刺激c-JUN / miR-4652-3p轴靶向NPC中的HIPK2。

更新日期:2020-07-08
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